TY - JOUR
T1 - TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets
AU - López-Jiménez, Cristóbal
AU - Chiu, Loraine L.Y.
AU - Waldman, Stephen D.
AU - Guilak, Farshid
AU - Koch, Thomas G.
N1 - Publisher Copyright:
© 2022
PY - 2022/6
Y1 - 2022/6
N2 - Objective: To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Methods: RT-PCR was performed to evaluate mRNA levels of chondrogenic, hypertrophic and candidate mechanoresponsive genes in equine neocartilage sheets exposed to pulses of the TRPV4 agonist (GSK101) at different concentrations (N = 10). Biochemical assays and mechanical tests (double indentation and unconfined compression) evaluated neocartilage properties (N = 5). Results: GSK101 treatment (1 nM) increased ACAN levels after treatment for 1-h per day for 3 days. No increase was detected for hypertrophic markers RUNX2, MMP13, MMP1, ALP or COL10A1 at this concentration. This treatment regimen also increased sGAG content and enhanced compressive properties compared to untreated controls. GSK101 showed no effect on candidate mechanoresponsive genes at the time-point of analysis. Conclusions: Chemical activation of TRPV4 signalling can be used as a strategy to enhance matrix synthesis and maturation of MSC-derived engineered neocartilage and augment its load-bearing capacity.
AB - Objective: To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Methods: RT-PCR was performed to evaluate mRNA levels of chondrogenic, hypertrophic and candidate mechanoresponsive genes in equine neocartilage sheets exposed to pulses of the TRPV4 agonist (GSK101) at different concentrations (N = 10). Biochemical assays and mechanical tests (double indentation and unconfined compression) evaluated neocartilage properties (N = 5). Results: GSK101 treatment (1 nM) increased ACAN levels after treatment for 1-h per day for 3 days. No increase was detected for hypertrophic markers RUNX2, MMP13, MMP1, ALP or COL10A1 at this concentration. This treatment regimen also increased sGAG content and enhanced compressive properties compared to untreated controls. GSK101 showed no effect on candidate mechanoresponsive genes at the time-point of analysis. Conclusions: Chemical activation of TRPV4 signalling can be used as a strategy to enhance matrix synthesis and maturation of MSC-derived engineered neocartilage and augment its load-bearing capacity.
KW - Mechanical properties
KW - Mesenchymal stromal cell
KW - Neocartilage
KW - TRPV4
UR - http://www.scopus.com/inward/record.url?scp=85152613573&partnerID=8YFLogxK
U2 - 10.1016/j.ocarto.2022.100263
DO - 10.1016/j.ocarto.2022.100263
M3 - Article
AN - SCOPUS:85152613573
SN - 2665-9131
VL - 4
JO - Osteoarthritis and Cartilage Open
JF - Osteoarthritis and Cartilage Open
IS - 2
M1 - 100263
ER -